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Brain Metastases in EGFR- and ALK-positive Non-Small Cell Lung Cancer: Outcomes of CNS Penetrant Tyrosine Kinase Inhibitors (TKIs) Alone versus in Combination with Radiation. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Thomas, N. J., Myall, N. J., Sun, F., Patil, T., Mushtaq, R., Yu, C., Sinha, S., Pollom, E. L., Nagpal, S., Camidge, D. R., Rusthoven, C. G., Braunstein, S. E., Wakelee, H. A., McCoach, C. E. 2021


INTRODUCTION: Management of central nervous system (CNS) metastases in patients with driver-mutated non-small cell lung cancer (NSCLC) has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next-generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases.METHODS: Data was retrospectively collected from 3 academic institutions. Two treatment groups (CNS-penetrant TKI alone vs TKI+CNS RT) were compared for both EGFR- and ALK-positive cohorts. Outcome variables included time to progression, time to intracranial progression, and time to treatment failure, measured from the date of initiation of CNS-penetrant TKI therapy.RESULTS: A total of 147 patients were included (EGFR n=94, ALK n=52, both n=1). In patients receiving radiation, larger metastases, neurological symptoms, and receipt of steroids were more common. There were no significant differences between TKI vs CNS RT+TKI groups for any of the study outcomes, including time to progression (8.5 vs 6.9 months, p=0.13 [EFGR] and 11.4 vs 13.4 months, p=0.98 [ALK]), time to intracranial progression (14.8 vs 20.5 months, p=0.51 [EGFR] and 18.1 vs 21.8 months, p=0.65 [ALK]), or time to treatment failure (13.8 vs 8.6 months, p=0.26 [EGFR] and 13.5 vs 23.2 months, p=0.95 [ALK]).CONCLUSION: These results provide preliminary evidence that intracranial activity of CNS-penetrant TKIs may enable local radiation to be deferred in appropriately selected patients without negatively impacting progression.

View details for DOI 10.1016/j.jtho.2021.08.009

View details for PubMedID 34455066